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Open AccessJournal ArticleDOI

hERG1a and hERG1b potassium channel subunits directly interact and preferentially form heteromeric channels

TLDR
HERG1b preferentially forms heteromeric ion channels with hERG1a at the plasma membrane, and multiple lines of evidence indicated a physical interaction between hERG 1a and hERG2b, consistent with them forming heteromerics channels.
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This article is published in Journal of Biological Chemistry.The article was published on 2017-12-29 and is currently open access. It has received 19 citations till now. The article focuses on the topics: Ion channel & Potassium channel.

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Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.

TL;DR: In an effort to encapsulate the breadth over which fluorescent biosensors have expanded, this work endeavored to assemble a comprehensive list of published engineered bios Sensors, and discusses many of the molecular designs utilized in their development.
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Drug-induced Proarrhythmia and Torsade de Pointes: A Primer for Students and Practitioners of Medicine and Pharmacy

TL;DR: This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety‐related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhalic liability.
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A microtranslatome coordinately regulates sodium and potassium currents in the human heart.

TL;DR: It is found that roughly half the hERG translational complexes contain SCN5A transcripts, and association and coordinate regulation of transcripts in discrete ‘microtranslatomes’ represents a new paradigm controlling electrical activity in heart and other excitable tissues.
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Fentanyl-Induced Block of hERG Channels Is Exacerbated by Hypoxia, Hypokalemia, Alkalosis, and the Presence of hERG1b.

TL;DR: It is demonstrated that heterologously expressed human ether a-go-go–related gene (hERG) 1a/1b channels, which more closely resemble rapidly activating delayed rectifier potassium current in the human heart, are blocked by fentanyl with a 3-fold greater potency than the previously studied hERG1a expressed alone.
References
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Journal ArticleDOI

Expression pattern of the ether-a-go-go-related (ERG) family proteins in the adult mouse central nervous system: evidence for coassembly of different subunits.

TL;DR: The finding that ERG proteins often have an overlapping expression suggests that neuronal ERG currents could be determined, at least in part, by heterotetrameric ERG channels, as demonstrated by showing that the two isoforms coassemble in mouse brain.
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Heteromeric assembly of human ether-à-go-go-related gene (hERG) 1a/1b channels occurs cotranslationally via N-terminal interactions.

TL;DR: HERG1 hetero-oligomerization occurs in the endoplasmic reticulum where co-expression of N-terminal fragments with hERG1 subunits disrupted oligomerization and core glycosylation, a cotranslational event.
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Direct interaction of eag domains and cyclic nucleotide-binding homology domains regulate deactivation gating in hERG channels.

TL;DR: It is found that most channels bearing individual alanine mutations in the S4–S5 linker were directly regulated by recombinant eag domains fused to a cyan fluorescent protein (N-eag-CFP) and had robust Förster resonance energy transfer (FRET).
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Rescue of Aberrant Gating by a Genetically Encoded PAS (Per-Arnt-Sim) Domain in Several Long QT Syndrome Mutant Human Ether-á-go-go-related Gene Potassium Channels

TL;DR: Results reveal a putative “gating face” in the PAS domain where mutations within this region form functional channels with altered gating properties, and show that NPAS is a general means for rescuing aberrant gating in hERG LQT2 mutant channels and may be a potential biological therapeutic.
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Dynamic conformational changes of extracellular S5-P linkers in the hERG channel.

TL;DR: It is proposed that the four S5–P linkers in a hERG channel can engage in dynamic conformational changes during channel gating, and interactions between S5-P linker from neighbouring subunits contribute importantly to channel inactivation.
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